1lds: Difference between revisions

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{{STRUCTURE_1lds|  PDB=1lds  |  SCENE=  }}  
{{STRUCTURE_1lds|  PDB=1lds  |  SCENE=  }}  


'''Crystal Structure of monomeric human beta-2-microglobulin'''
===Crystal Structure of monomeric human beta-2-microglobulin===




==Overview==
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Dissociation of human beta-2-microglobulin (beta(2)m) from the heavy chain of the class I HLA complex is a critical first step in the formation of amyloid fibrils from this protein. As a consequence of renal failure, the concentration of circulating monomeric beta(2)m increases, ultimately leading to deposition of the protein into amyloid fibrils and development of the disorder, dialysis-related amyloidosis. Here we present the crystal structure of a monomeric form of human beta(2)m determined at 1.8-A resolution that reveals remarkable structural changes relative to the HLA-bound protein. These involve the restructuring of a beta bulge that separates two short beta strands to form a new six-residue beta strand at one edge of this beta sandwich protein. These structural changes remove key features proposed to have evolved to protect beta sheet proteins from aggregation [Richardson, J. &amp; Richardson, D. (2002) Proc. Natl. Acad. Sci. USA 99, 2754-2759] and replaces them with an aggregation-competent surface. In combination with solution studies using (1)H NMR, we show that the crystal structure presented here represents a rare species in solution that could provide important clues about the mechanism of amyloid formation from the normally highly soluble native protein.
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{{ABSTRACT_PUBMED_12119416}}


==Disease==
==Disease==
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[[Category: Trinh, C H.]]
[[Category: Trinh, C H.]]
[[Category: Immunoglobulin constant domain]]
[[Category: Immunoglobulin constant domain]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 23:49:41 2008''
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 2 12:47:30 2008''

Revision as of 09:47, 2 July 2008

File:1lds.png

Template:STRUCTURE 1lds

Crystal Structure of monomeric human beta-2-microglobulin

Template:ABSTRACT PUBMED 12119416

Disease

Known disease associated with this structure: Hypoproteinemia, hypercatabolic OMIM:[109700]

About this Structure

1LDS is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Crystal structure of monomeric human beta-2-microglobulin reveals clues to its amyloidogenic properties., Trinh CH, Smith DP, Kalverda AP, Phillips SE, Radford SE, Proc Natl Acad Sci U S A. 2002 Jul 23;99(15):9771-6. Epub 2002 Jul 15. PMID:12119416

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